The 5-year survival from lung cancer has kept pace with the improvement in 5-year survival from all cancers over the last 40 years. Yet, it remains disappointingly low at ~15%. This improvement in 5-year survival is a result of heightened awareness, better technology for detection, better selection of patients for various therapeutic options, and the selective use of palliative interventions. However, lung cancer mortality remains extraordinarily high, and it is the benchmark by which future generations will judge our success in effectively combating this disease. The Moffitt Cancer Center SPORE in Lung Cancer will 1) elucidate mechanisms of action of crucial molecules in lung carcinogenesis and tumor progression and investigate their impact on therapeutic efficacy and 2) prospectively assess the clinical utility of the molecules for therapeutic and prevention interventions. Our ultimate goal is to change the standard of care for people at risk for and with lung cancer. The SPORE has five translational research projects, three cores, a developmental research program, and a career development program. The projects are: 1) E2Fs Impact on Therapeutic Efficacy (Cress, Chen & Bepler) 2) RRM1 in the Management of Lung Cancer (Bepler, Cress & Simon) 3) Antitumor Mechanisms of Src Inhibitors in Lung Cancer (Haura, Cheng & Pledger) 4) Lung Cancer Chemoprevention with Enzastaurin (Bepler & Alexandrow) 5) p53-Based Vaccine for Small Cell Lung Cancer (Gabrilovich & Antonia) They are support by: A) Tissue Procurement, Pathology, and Bioinformatics Core (Altiok & Fenstermacher) B) Clinical Trials & Biostatistics Core (Simon, Schell & Bepler) C) Administration & Patient Advocacy Core (Bepler, Cress & Quinn). The SPORE also has Developmental Research & Career Development Programs. This SPORE will be firmly integrated into the H. Lee Moffitt Cancer Center and Research Institute, a free-standing, NCI designated Comprehensive Cancer in Tampa, Florida.